To assess safety and tolerability of the β3-adrenoreceptor agonist mirabegron and antimuscarinics using a large integrated database (IDB) of patient data.

The IDB included all patients who received ≥1 dose of monotherapy: mirabegron 25 mg or 50 mg, solifenacin 2.5 mg, 5 mg, or 10 mg, tolterodine ER 4 mg, or placebo for overactive bladder (OAB) in 10 global, double-blind, 12-week phase 2–4 mirabegron studies. The studies were carried out in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki (1996). Patients provided written informed consent. Demographic characteristics and baseline data are presented for the total mirabegron, total antimuscarinic and placebo groups. Safety was assessed by evaluation of treatment-emergent adverse events (TEAEs).

The IDB comprised: total mirabegron, n=5244 (mirabegron 25 mg, n=1311; mirabegron 50 mg, n=3933); total antimuscarinics, n=2999 (solifenacin 2.5 mg, n=79; solifenacin 5 mg, n=1513; solifenacin 10 mg, n=78; tolterodine ER 4 mg, n=1329); placebo, n=3018 patients. The total mirabegron group was 75.4% female, 71.7% white, mean (SD) age 57.4 (13.5) years; 45.8% had urgency incontinence, 26.8% frequency/urgency without incontinence, 27.4% mixed stress/urgency incontinence. This symptom distribution was similar across treatment groups apart from the total antimuscarinics group, which had a 6–7% higher proportion of frequency/urgency without incontinence and 6–7% lower mixed incontinence versus the total mirabegron and placebo groups. In the total mirabegron group, 47.3% were OAB treatment naïve versus 43.0% in the total antimuscarinics group and 58.3% in the placebo group. In mirabegron patients with prior OAB treatment, 69.0% had discontinued at least 1 prior treatment due to lack of efficacy and 18.2% due to poor tolerability. Frequency of hypertension at baseline was similar for all groups (26–28%). 

Treatment discontinuation was balanced across the active treatment groups, with slightly more discontinuations occurring in the placebo group (90.5% and 91.7% of patients in the total mirabegron and total antimuscarinics group completed treatment compared with 88.6% of patients in the placebo group). Percentages reporting TEAEs and common TEAEs (those with ≥1% in any aggregate active treatment group) are shown in the Table. Urinary retention was <1% for all groups.

Percentages reporting TEAEs were generally similar across treatment groups, although slightly more drug-related AEs were reported for the total antimuscarinics group (21.4%) than for the total mirabegron group (17.0%). Dry mouth was higher in the total antimuscarinics group versus the total mirabegron and placebo groups; constipation was similar between groups. Frequency of palpitations and tachycardia was low across treatment groups (<1% in all groups), as were treatment-emergent hypertension (3.2–3.9%) and urinary tract infection (1.7–2.1%).

TEAEs were similar for active treatment groups, although frequency of dry mouth was highest for the total antimuscarinics group. Withdrawal from treatment was low across all groups. Overall frequency of cardiac and cognitive TEAEs was low. This large IDB reaffirms the safety of the OAB medications studied.